Jonathan M. Irish, Ph.D.

Assistant Professor

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Faculty Appointments
Assistant Professor of Cell & Developmental Biology Assistant Professor of Pathology, Microbiology and Immunology
Ph.D., Cancer Biology, Stanford University, Stanford, CaliforniaB.S., University of Michigan, Ann Arbor, Michigan
Office Address
740B Preston Research Building
Irish Lab, Vanderbilt University
2220 Pierce Ave
Nashville, TN 37232-6840
Research Description
A central goal of our research at Vanderbilt is to understand how changes at the single cell level alter signaling in healthy cells and lead to therapy resistant populations in human diseases. In the Irish Lab, we use new tools and computational approaches to do basic and translational research in human cancer and immunology.

In addition to making discoveries at the frontier of human genetics and immunology, we aspire to use knowledge of cell signaling to create therapeutic technologies and to guide clinical decisions. In the long term, great potential exists to detect disease earlier and to tailor a patient’s therapy to the biological alterations detected in the cells of their disease. By better understanding biological systems which control development and cell-cell interactions in healthy and diseased contexts, we can learn to program cells to become therapeutic agents or target malignant signaling events to specifically kill cancer cells.

Profile on Google Scholar:

Projects (updated Fall 2017):  For trainees who join the lab, projects will be tailored to fit interests and available opportunities. Active research areas include: 1) neural stem cell and immune cell signaling interactions in brain tumors, 2) creating and applying machine learning algorithms that identify healthy and malignant human cell types, and 3) identifying immune mechanisms of therapy response in human bone marrow, blood, germinal center, and tissue microenvironments. Rotations begin with training in our core technologies, such as phospho-specific flow cytometry, mass cytometry, and single cell data analysis.
Research Keywords
We study how signaling controls human cell identity. [ Keywords: Cancer, immunology, precision medicine, computational biology, machine learning, cell signaling, chemical biology, single cell tools. ]
Doxie DB, Greenplate AR, Gandelman JS, Diggins KE, Roe CE, Dahlman KB, Sosman JA, Kelley MC, Irish JM. BRAF and MEK inhibitor therapy eliminates nestin expressing melanoma cells in human tumors. Pigment Cell Melanoma Res [print-electronic]. 2018 May 5/19/2018; PMID: 29778085, DOI: 10.1111/pcmr.12712, ISSN: 1755-148X.

Diggins KE, Gandelman JS, Roe CE, Irish JM. Generating Quantitative Cell Identity Labels with Marker Enrichment Modeling (MEM). Curr Protoc Cytom. 2018 Jan 1/18/2018; 83: 10.21.1-10.21.28. PMID: 29345329, PMCID: PMC5774653, DOI: 10.1002/cpcy.34, ISSN: 1934-9300.

Earl DC, Ferrell PB, Leelatian N, Froese JT, Reisman BJ, Irish JM, Bachmann BO. Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics. Nat Commun. 2018 Jan 1/2/2018; 9(1): 39. PMID: 29295987, PII: 10.1038/s41467-017-02470-8, DOI: 10.1038/s41467-017-02470-8, ISSN: 2041-1723.

Josefsson SE, Huse K, Kolstad A, Beiske K, Pende D, Steen CB, Inderberg EM, Lingjærde OC, Østenstad B, Smeland EB, Levy R, Irish JM, Myklebust JH. T cells expressing checkpoint receptor TIGIT are enriched in follicular lymphoma tumors and characterized by reversible suppression of T-cell receptor signaling. Clin. Cancer Res [print-electronic]. 2017 Dec 12/7/2017; PMID: 29217528, PII: 1078-0432.CCR-17-2337, DOI: 10.1158/1078-0432.CCR-17-2337, ISSN: 1078-0432.

Roussel M, Irish JM, Menard C, Lhomme F, Tarte K, Fest T. Regulatory myeloid cells: an underexplored continent in B-cell lymphomas. Cancer Immunol. Immunother [print-electronic]. 2017 Jul 7/8/2017; PMID: 28689360, PII: 10.1007/s00262-017-2036-5, DOI: 10.1007/s00262-017-2036-5, ISSN: 1432-0851.

Siska PJ, Beckermann KE, Mason FM, Andrejeva G, Greenplate AR, Sendor AB, Chiang YJ, Corona AL, Gemta LF, Vincent BG, Wang RC, Kim B, Hong J, Chen CL, Bullock TN, Irish JM, Rathmell WK, Rathmell JC. Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma. JCI Insight [print-electronic]. 2017 Jun 6/15/2017; 2(12): PMID: 28614802, PMCID: PMC5470888, PII: 93411, DOI: 10.1172/jci.insight.93411, ISSN: 2379-3708.

Roussel M, Ferrell PB, Greenplate AR, Lhomme F, Le Gallou S, Diggins KE, Johnson DB, Irish JM. Mass cytometry deep phenotyping of human mononuclear phagocytes and myeloid-derived suppressor cells from human blood and bone marrow. J. Leukoc. Biol [print-electronic]. 2017 Apr 4/11/2017; PMID: 28400539, PII: jlb.5MA1116-457R, DOI: 10.1189/jlb.5MA1116-457R, ISSN: 1938-3673.

Leelatian N, Doxie DB, Greenplate AR, Sinnaeve J, Ihrie RA, Irish JM. Preparing Viable Single Cells from Human Tissue and Tumors for Cytomic Analysis. Curr Protoc Mol Biol. 2017 Apr 4/3/2017; 118: 25C.1.1-25C.1.23. PMID: 28369679, DOI: 10.1002/cpmb.37, ISSN: 1934-3647.

Diggins KE, Greenplate AR, Leelatian N, Wogsland CE, Irish JM. Characterizing cell subsets using marker enrichment modeling. Nat. Methods [print-electronic]. 2017 Mar; 14(3): 275-8. PMID: 28135256, PMCID: PMC5330853, PII: nmeth.4149, DOI: 10.1038/nmeth.4149, ISSN: 1548-7105.

Udyavar AR, Wooten DJ, Hoeksema M, Bansal M, Califano A, Estrada L, Schnell S, Irish JM, Massion PP, Quaranta V. Novel Hybrid Phenotype Revealed in Small Cell Lung Cancer by a Transcription Factor Network Model That Can Explain Tumor Heterogeneity. Cancer Res [print-electronic]. 2017 Mar 3/1/2017; 77(5): 1063-74. PMID: 27932399, PII: 0008-5472.CAN-16-1467, DOI: 10.1158/0008-5472.CAN-16-1467, ISSN: 1538-7445.

Myklebust JH, Brody J, Kohrt HE, Kolstad A, Czerwinski DK, Wälchli S, Green MR, Trøen G, Liestøl K, Beiske K, Houot R, Delabie J, Alizadeh AA, Irish JM, Levy R. Distinct patterns of B-cell receptor signaling in non-Hodgkin lymphomas identified by single-cell profiling. Blood [print-electronic]. 2017 Feb 2/9/2017; 129(6): 759-70. PMID: 28011673, PMCID: PMC5301824, PII: blood-2016-05-718494, DOI: 10.1182/blood-2016-05-718494, ISSN: 1528-0020.

Wogsland CE, Greenplate AR, Kolstad A, Myklebust JH, Irish JM, Huse K. Mass Cytometry of Follicular Lymphoma Tumors Reveals Intrinsic Heterogeneity in Proteins Including HLA-DR and a Deficit in Nonmalignant Plasmablast and Germinal Center B-Cell Populations. Cytometry B Clin Cytom. 2017 Jan; 92(1): 79-87. PMID: 27933753, DOI: 10.1002/cyto.b.21498, ISSN: 1552-4957.

Leelatian N, Doxie DB, Greenplate AR, Mobley BC, Lehman JM, Sinnaeve J, Kauffmann RM, Werkhaven JA, Mistry AM, Weaver KD, Thompson RC, Massion PP, Hooks MA, Kelley MC, Chambless LB, Ihrie RA, Irish JM. Single cell analysis of human tissues and solid tumors with mass cytometry. Cytometry B Clin Cytom [print-electronic]. 2017 Jan; 92(1): 68-78. PMID: 27598832, DOI: 10.1002/cyto.b.21481, ISSN: 1552-4957.

Simmons AJ, Scurrah CR, McKinley ET, Herring CA, Irish JM, Washington MK, Coffey RJ, Lau KS. Impaired coordination between signaling pathways is revealed in human colorectal cancer using single-cell mass cytometry of archival tissue blocks. Sci Signal. 2016 Oct 10/11/2016; 9(449): rs11. PMID: 27729552, PMCID: PMC5111815, PII: 9/449/rs11, DOI: 10.1126/scisignal.aah4413, ISSN: 1937-9145.

Kordasti S, Costantini B, Seidl T, Perez Abellan P, Martinez Llordella M, McLornan D, Diggins KE, Kulasekararaj A, Benfatto C, Feng X, Smith A, Mian SA, Melchiotti R, de Rinaldis E, Ellis R, Petrov N, Povoleri GA, Chung SS, Thomas NS, Farzaneh F, Irish JM, Heck S, Young NS, Marsh JC, Mufti GJ. Deep phenotyping of Tregs identifies an immune signature for idiopathic aplastic anemia and predicts response to treatment. Blood [print-electronic]. 2016 Sep 9/1/2016; 128(9): 1193-205. PMID: 27281795, PMCID: PMC5009512, PII: blood-2016-03-703702, DOI: 10.1182/blood-2016-03-703702, ISSN: 1528-0020.

Simmons AJ, Banerjee A, McKinley ET, Scurrah CR, Herring CA, Gewin LS, Masuzaki R, Karp SJ, Franklin JL, Gerdes MJ, Irish JM, Coffey RJ, Lau KS. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-a-induced apoptosis in vivo. Mol. Syst. Biol. 2016 Aug 8/29/2016; 12(8): 881. PMID: 27574014, PMCID: PMC5119492, ISSN: 1744-4292.

Greenplate AR, Johnson DB, Ferrell PB, Irish JM. Systems immune monitoring in cancer therapy. Eur. J. Cancer [print-electronic]. 2016 Jul; 61: 77-84. PMID: 27155446, PMCID: PMC4885747, PII: S0959-8049(16)32047-0, DOI: 10.1016/j.ejca.2016.03.085, ISSN: 1879-0852.

Greenplate AR, Johnson DB, Roussel M, Savona MR, Sosman JA, Puzanov I, Ferrell PB, Irish JM. Myelodysplastic Syndrome Revealed by Systems Immunology in a Melanoma Patient Undergoing Anti-PD-1 Therapy. Cancer Immunol Res [print-electronic]. 2016 Mar 3/10/2016; PMID: 26966176, PII: 2326-6066.CIR-15-0213, DOI: 10.1158/2326-6066.CIR-15-0213, ISSN: 2326-6074.

Chong KM, Leelatian N, Deguire SM, Brockman AA, Earl D, Ihrie RA, Irish JM, Bachmann BO, Sulikowski GA. The use of fluorescently-tagged apoptolidins in cellular uptake and response studies. J. Antibiot [print-electronic]. 2016 Mar 3/9/2016; PMID: 26956792, PII: ja201622, DOI: 10.1038/ja.2016.22, ISSN: 0021-8820.

Johnson DB, Estrada MV, Salgado R, Sanchez V, Doxie DB, Opalenik SR, Vilgelm AE, Feld E, Johnson AS, Greenplate AR, Sanders ME, Lovly CM, Frederick DT, Kelley MC, Richmond A, Irish JM, Shyr Y, Sullivan RJ, Puzanov I, Sosman JA, Balko JM. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Nat Commun. 2016; 7: 10582. PMID: 26822383, PMCID: PMC4740184, PII: ncomms10582, DOI: 10.1038/ncomms10582, ISSN: 2041-1723.

Ferrell PB, Diggins KE, Polikowsky HG, Mohan SR, Seegmiller AC, Irish JM. High-Dimensional Analysis of Acute Myeloid Leukemia Reveals Phenotypic Changes in Persistent Cells during Induction Therapy. PLoS ONE. 2016; 11(4): e0153207. PMID: 27074138, PMCID: PMC4830605, PII: PONE-D-15-20447, DOI: 10.1371/journal.pone.0153207, ISSN: 1932-6203.

Shah AT, Diggins KE, Walsh AJ, Irish JM, Skala MC. In Vivo Autofluorescence Imaging of Tumor Heterogeneity in Response to Treatment. Neoplasia. 2015 Dec; 17(12): 862-70. PMID: 26696368, PII: S1476-5586(15)00143-8, DOI: 10.1016/j.neo.2015.11.006, ISSN: 1476-5586.

Nicholas KJ, Greenplate AR, Flaherty DK, Matlock BK, Juan JS, Smith RM, Irish JM, Kalams SA. Multiparameter analysis of stimulated human peripheral blood mononuclear cells: A comparison of mass and fluorescence cytometry. Cytometry A [print-electronic]. 2015 Nov 11/24/2015; PMID: 26599989, DOI: 10.1002/cyto.a.22799, ISSN: 1552-4930.

Polikowsky HG, Wogsland CE, Diggins KE, Huse K, Irish JM. Cutting Edge: Redox Signaling Hypersensitivity Distinguishes Human Germinal Center B Cells. J. Immunol [print-electronic]. 2015 Aug 8/15/2015; 195(4): 1364-7. PMID: 26157177, PMCID: PMC4530023, PII: jimmunol.1500904, DOI: 10.4049/jimmunol.1500904, ISSN: 1550-6606.

Diggins KE, Ferrell PB, Irish JM. Methods for discovery and characterization of cell subsets in high dimensional mass cytometry data. Methods [print-electronic]. 2015 Jul 7/1/2015; 82: 55-63. PMID: 25979346, PMCID: PMC4468028, PII: S1046-2023(15)00199-1, DOI: 10.1016/j.ymeth.2015.05.008, ISSN: 1095-9130.

Green MR, Kihira S, Liu CL, Nair RV, Salari R, Gentles AJ, Irish J, Stehr H, Vicente-Dueñas C, Romero-Camarero I, Sanchez-Garcia I, Plevritis SK, Arber DA, Batzoglou S, Levy R, Alizadeh AA. Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2015 Mar 3/10/2015; 112(10): E1116-25. PMID: 25713363, PMCID: PMC4364211, PII: 1501199112, DOI: 10.1073/pnas.1501199112, ISSN: 1091-6490.

Karr JR, Guturu H, Chen EY, Blair SL, Irish JM, Kotecha N, Covert MW. NetworkPainter: dynamic intracellular pathway animation in Cytobank. BMC Bioinformatics. 2015; 16: 172. PMID: 26003204, PMCID: PMC4491883, PII: 10.1186/s12859-015-0602-4, DOI: 10.1186/s12859-015-0602-4, ISSN: 1471-2105.

Simmons AJ, Banerjee A, McKinley ET, Scurrah CR, Herring CA, Gewin LS, Masuzaki R, Karp SJ, Franklin JL, Gerdes MJ, Irish JM, Coffey RJ, Lau KS. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-a-induced apoptosis in vivo. Mol. Syst. Biol. 2015; 11(10): 835. PMID: 26519361, PMCID: PMC4631206, ISSN: 1744-4292.

Leelatian N, Diggins KE, Irish JM. Characterizing Phenotypes and Signaling Networks of Single Human Cells by Mass Cytometry. Methods Mol. Biol. 2015; 1346: 99-113. PMID: 26542718, PMCID: PMC4656023, DOI: 10.1007/978-1-4939-2987-0_8, ISSN: 1940-6029.

Irish JM. Beyond the age of cellular discovery. Nature immunology. 2014 Dec; 15(12) Sect. 1095,7.

Pyne S, Lee SX, Wang K, Irish J, Tamayo P, Nazaire MD, Duong T, Ng SK, Hafler D, Levy R, Nolan GP, Mesirov J, McLachlan GJ. Joint modeling and registration of cell populations in cohorts of high-dimensional flow cytometric data. PLoS ONE. 2014; 9(7): e100334. PMID: 24983991, PMCID: PMC4077578, PII: PONE-D-13-55136, DOI: 10.1371/journal.pone.0100334, ISSN: 1932-6203.

Irish JM, Doxie DB. High-dimensional single-cell cancer biology. Curr. Top. Microbiol. Immunol. 2014; 377: 1-21. PMID: 24671264, PMCID: PMC4216808, DOI: 10.1007/82_2014_367, ISSN: 0070-217X.

Green MR, Gentles AJ, Nair RV, Irish JM, Kihira S, Liu CL, Kela I, Hopmans ES, Myklebust JH, Ji H, Plevritis SK, Levy R, Alizadeh AA. Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. Blood [print-electronic]. 2013 Feb 2/28/2013; 121(9): 1604-11. PMID: 23297126, PMCID: PMC3587323, PII: blood-2012-09-457283, DOI: 10.1182/blood-2012-09-457283, ISSN: 1528-0020.

Myklebust JH, Irish JM, Brody J, Czerwinski DK, Houot R, Kohrt HE, Timmerman J, Said J, Green MR, Delabie J, Kolstad A, Alizadeh AA, Levy R. High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells. Blood [print-electronic]. 2013 Feb 2/21/2013; 121(8): 1367-76. PMID: 23297127, PMCID: PMC3578953, PII: blood-2012-04-421826, DOI: 10.1182/blood-2012-04-421826, ISSN: 1528-0020.

Blix ES, Irish JM, Husebekk A, Delabie J, Tierens AM, Myklebust JH, Kolstad A. Altered BCR and CD40 signalling are associated with clinical outcome in small lymphocytic lymphoma/chronic lymphocytic leukaemia and marginal zone lymphoma patients [letter]. Br. J. Haematol [print-electronic]. 2012 Dec; 159(5): 604-8. PMID: 23043253, PMCID: PMC3767388, DOI: 10.1111/bjh.12073, ISSN: 1365-2141.

Blix ES, Irish JM, Husebekk A, Delabie J, Forfang L, Tierens AM, Myklebust JH, Kolstad A. Phospho-specific flow cytometry identifies aberrant signaling in indolent B-cell lymphoma. BMC Cancer. 2012; 12: 478. PMID: 23072591, PMCID: PMC3519597, PII: 1471-2407-12-478, DOI: 10.1186/1471-2407-12-478, ISSN: 1471-2407.

Irish JM, Myklebust JH, Alizadeh AA, Houot R, Sharman JP, Czerwinski DK, Nolan GP, Levy R. B-cell signaling networks reveal a negative prognostic human lymphoma cell subset that emerges during tumor progression. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2010 Jul 7/20/2010; 107(29): 12747-54. PMID: 20543139, PMCID: PMC2919949, PII: 1002057107, DOI: 10.1073/pnas.1002057107, ISSN: 1091-6490.

Kotecha N, Krutzik PO, Irish JM. Web-based analysis and publication of flow cytometry experiments. Curr Protoc Cytom. 2010 Jul; Chapter 10: Unit10.17. PMID: 20578106, PMCID: PMC4208272, DOI: 10.1002/0471142956.cy1017s53, ISSN: 1934-9300.

Houot R, Goldstein MJ, Kohrt HE, Myklebust JH, Alizadeh AA, Lin JT, Irish JM, Torchia JA, Kolstad A, Chen L, Levy R. Therapeutic effect of CD137 immunomodulation in lymphoma and its enhancement by Treg depletion. Blood [print-electronic]. 2009 Oct 10/15/2009; 114(16): 3431-8. PMID: 19641184, PMCID: PMC2765679, PII: blood-2009-05-223958, DOI: 10.1182/blood-2009-05-223958, ISSN: 1528-0020.

Hammer MM, Kotecha N, Irish JM, Nolan GP, Krutzik PO. WebFlow: a software package for high-throughput analysis of flow cytometry data. Assay Drug Dev Technol. 2009 Feb; 7(1): 44-55. PMID: 19187010, PMCID: PMC2956679, PII: 10.1089/adt.2008.174, DOI: 10.1089/adt.2008.174, ISSN: 1540-658X.

Kotecha N, Flores NJ, Irish JM, Simonds EF, Sakai DS, Archambeault S, Diaz-Flores E, Coram M, Shannon KM, Nolan GP, Loh ML. Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates. Cancer Cell. 2008 Oct 10/7/2008; 14(4): 335-43. PMID: 18835035, PMCID: PMC2647559, PII: S1535-6108(08)00293-6, DOI: 10.1016/j.ccr.2008.08.014, ISSN: 1878-3686.

Van Meter ME, Díaz-Flores E, Archard JA, Passegué E, Irish JM, Kotecha N, Nolan GP, Shannon K, Braun BS. K-RasG12D expression induces hyperproliferation and aberrant signaling in primary hematopoietic stem/progenitor cells. Blood [print-electronic]. 2007 May 5/1/2007; 109(9): 3945-52. PMID: 17192389, PMCID: PMC1874575, PII: blood-2006-09-047530, DOI: 10.1182/blood-2006-09-047530, ISSN: 0006-4971.

Irish JM, Anensen N, Hovland R, Skavland J, Børresen-Dale AL, Bruserud O, Nolan GP, Gjertsen BT. Flt3 Y591 duplication and Bcl-2 overexpression are detected in acute myeloid leukemia cells with high levels of phosphorylated wild-type p53. Blood [print-electronic]. 2007 Mar 3/15/2007; 109(6): 2589-96. PMID: 17105820, PII: blood-2006-02-004234, DOI: 10.1182/blood-2006-02-004234, ISSN: 0006-4971.

Irish JM, Czerwinski DK, Nolan GP, Levy R. Altered B-cell receptor signaling kinetics distinguish human follicular lymphoma B cells from tumor-infiltrating nonmalignant B cells. Blood [print-electronic]. 2006 Nov 11/1/2006; 108(9): 3135-42. PMID: 16835385, PMCID: PMC1895530, PII: blood-2006-02-003921, DOI: 10.1182/blood-2006-02-003921, ISSN: 0006-4971.

Irish JM, Czerwinski DK, Nolan GP, Levy R. Kinetics of B cell receptor signaling in human B cell subsets mapped by phosphospecific flow cytometry. J. Immunol. 2006 Aug 8/1/2006; 177(3): 1581-9. PMID: 16849466, PII: 177/3/1581, ISSN: 0022-1767.

Irish JM, Kotecha N, Nolan GP. Mapping normal and cancer cell signalling networks: towards single-cell proteomics. Nat. Rev. Cancer. 2006 Feb; 6(2): 146-55. PMID: 16491074, PII: nrc1804, DOI: 10.1038/nrc1804, ISSN: 1474-175X.

Irish JM, Hovland R, Krutzik PO, Perez OD, Bruserud Ø, Gjertsen BT, Nolan GP. Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell. 2004 Jul 7/23/2004; 118(2): 217-28. PMID: 15260991, PII: S0092867404006282, DOI: 10.1016/j.cell.2004.06.028, ISSN: 0092-8674.

Krutzik PO, Irish JM, Nolan GP, Perez OD. Analysis of protein phosphorylation and cellular signaling events by flow cytometry: techniques and clinical applications. Clin. Immunol. 2004 Mar; 110(3): 206-21. PMID: 15047199, PII: S1521661603003097, DOI: 10.1016/j.clim.2003.11.009, ISSN: 1521-6616.

Armstrong JS, Steinauer KK, Hornung B, Irish JM, Lecane P, Birrell GW, Peehl DM, Knox SJ. Role of glutathione depletion and reactive oxygen species generation in apoptotic signaling in a human B lymphoma cell line. Cell Death Differ. 2002 Mar; 9(3): 252-63. PMID: 11859408, DOI: 10.1038/sj.cdd.4400959, ISSN: 1350-9047.